Field of the Invention
The invented method relates generally to the manufacture of an injection device, and, more specifically, to a method of manufacturing a miniaturized device for injection of a therapeutic agent, such as a vaccine by an individual without medical training.
Description of Related Art
Current vaccination programs have numerous financial and logistical problems. In emerging countries, public health officials have, so far, been largely unsuccessful in carrying out large-scale vaccination initiatives. One reason for the lack of success stems from the logistical difficulties in transporting large populations to a limited number of distant immunization clinics where professionals have sufficient expertise to perform the inoculation. While charitable organizations and non-governmental organizations provide considerable amounts of money to cover vaccine costs, the lack of infrastructure has prevented these vaccines from reaching many rural populations.
In developed countries, doctor shortages are increasing and long standing policy issues have made the distribution of vaccines complex. In times of increased need for vaccines, vaccine distribution is often managed “on-the-fly”. As the average population in these developed countries continues to increase, the need for vaccinations in response to flu outbreak will certainly increase. Further, the existing immunization infrastructures are insufficient for responding to pandemic situations. World health experts continue to caution that as global integration increases, the possibility of a rapidly spreading world-wide flu pandemic continues to increase.
The problems associated with providing immunization on a large scale generally result from a combination of: (1) how vaccinations are administered; and (2) currently available injection devices. Receiving a vaccine or drug through injection most typically requires at least one appointment with a medical provider such as a General Practitioner (GP). The injection is generally performed by a trained professional such as a nurse. In many countries, the cost of a GP appointment, not including the cost of the drug or injection itself, is significant. Further, many countries are currently experiencing a shortage of GPs and other trained medical professionals. This shortage could be alleviated in part if medical professionals spent less time performing trivial procedures, such as injections, and more time diagnosing and treating more complex medical conditions. It is evident that significant savings in time and expense could be realized if untrained individuals could perform injections of vaccines and other therapeutic agents on themselves.
A wide variety of hypodermic injection devices for fluid injections are commercially available. Most hypodermic injections are intended to be intramuscular, requiring that a hypodermic needle penetrates through an individual's skin layer and subcutaneous tissue and into the muscle. Needles of this type generally cause pain, damage to the skin at the site of insertion, and bleeding, which increases the risk of disease transmission and infection at the wound site. Intramuscular injections also generally require administration by one trained in needle use. Problems of pain, wound formation, and the general skill required to perform the injection mean that intramuscular injections are difficult to perform outside of a medical facility and especially difficult for untrained individuals to perform self-injections.
An alternative delivery technique is the transdermal patch, which relies on diffusion of a drug across the skin. However, transdermal delivery devices are not useful for many drugs, due to the poor permeability (i.e., effective barrier properties) of the skin. The rate of diffusion depends in part on the size and hydrophilicity of the drug molecules and the concentration gradient across skin layers. In fact, few drugs have the necessary properties to be effectively delivered through the skin by passive diffusion. While providing varying degrees of enhancement can increase permeability for some substances, these techniques are not suitable for all types of drugs. In some cases, transdermal drug delivery is also painful and inconvenient for users.
A second alternative drug delivery possibility is a mini-needle syringe. Mini-needle syringes allow for intradermal injection of a drug at clinically relevant rates through one or more layers of skin with minimal damage, pain, or irritation to the surrounding tissue. Mini-needle syringes include a needle shaft having a cross-sectional dimension of between about 1 μm and 500 μm. In many cases, the puncture site formed by a mini-needle is less than about 0.2 μm in diameter. The small diameter of the puncture site reduces pain and increases healing time, significantly reducing the possibility of infection. An example of such an intradermal delivery device and needle assembly is disclosed in U.S. Pat. No. 6,494,865 assigned to Becton, Dickinson and Company and incorporated herein by reference. However, it is recognized that while mini-needle syringes effectively reduce pain, many individuals are, nevertheless, intimidated by the prospect of performing an injection on themselves. Specifically, research indicates that individuals without medical training are still intimidated by the prospect of performing an injection on themselves. Thus, it can be concluded that it is the fear and anticipation of the injection process, rather than the pain itself, that prevents many individuals from performing injections on themselves.
More recently still, miniaturized drug delivery devices based on patch-like designs have been envisioned which further miniaturize the needle assembly. These devices are manufactured using micro-scale manufacturing techniques developed for the semiconductor industry and are suitable for mass production. Typically, such devices involve microneedles produced from a substrate such as a silicon base by, for example, press extrusion techniques in which force exerted on a top portion of the substrate produces a pointed tip extending from the base of the substrate. Often the tip portions of the microneedles are shaped and dimensioned to carry a biologically active substance. The plurality of needles pierces and penetrates into target cells within tissue, so that the biological substance is transferred from the tip portion and deposited within the target cells.
However, such tip loading is not effective to deliver a precisely metered dose of a biologically active substance. Generally, medical treatment methodologies that include injection into a patient require precisely controlling the amount of drug delivered which cannot be accomplished with tip coating. Further, microneedles produced by this process pierce the stratum corteum of the skin, but do not extend into the dermis. Accordingly, such microneedles are generally unable to facilitate delivery of drugs which cannot diffuse through the dermis layer of skin. Vaccines are an example of a therapeutic agent that cannot diffuse through the epidermis or stratum corteum.
Therefore, it would be desirable to provide an injection device and method of manufacture thereof for intradermal delivery of a therapeutic or preventative agent configured for self-injection.